SAD and MAD of Inhaled AR-501 in Health Adults and P. Aeruginosa Infected Cystic Fibrosis Subjects

NCT03669614 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: AR-501-001
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 25

Brief Summary

This is a Phase 1/2a randomized, double-blind, two-part, dose-ascending, multicenter study of AR-501 (gallium citrate) solution, administered via inhalation, in healthy adult and P. aeruginosa infected cystic fibrosis (CF) subjects. Phase 1 of the study in HV subjects will consist of a single-ascending-dose (SAD) cohort, followed by the HV multiple-ascending-dose (MAD) cohort. Phase 2a of the study in CF subjects will consist of a MAD study design. The study will evaluate the safety and pharmacokinetic (PK) profile of single and repeat administrations of inhaled AR-501 solution in healthy adults, and the safety, PK and efficacy of repeat administrations of inhaled AR-501 solution in P. aeruginosa infected CF subjects.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Gallium Citrate; Pseudomonas Aeruginosa

Outcome Measures

Primary Outcomes (2)

• Clinical safety profile (adverse events) - Single Ascending Dose

  Evaluation of adverse events in HV subjects

  28 days following dose administration

• Clinical safety profile (adverse events) - Multiple Ascending Dose

  Evaluation of adverse events in HV and CF subjects

  up to 28 days after last dose administration

Secondary Outcomes (14)

• Pharmacokinetics (PK) Profile - SAD Cmax

  28 days following dose administration

• Pharmacokinetics (PK) Profile - SAD Tmax

  28 days following dose administration

• Pharmacokinetics (PK) Profile - SAD AUC0-inf

  28 days following dose administration

• Pharmacokinetics (PK) Profile - SAD AUC0-last

  28 days following dose administration

• Pharmacokinetics (PK) Profile - SAD λz

  28 days following dose administration

Study Arms (2)

AR-501 inhaled

EXPERIMENTAL

Four doses (low, medium, high, top) of inhaled AR-501 will be used.

Drug: Inhaled AR-501

inhaled AR-501 Placebo

PLACEBO COMPARATOR

Four doses (low, medium, high, top) of inhaled placebo will be used

Drug: Inhaled Placebo

Interventions

Inhaled AR-501 DRUG

single and multiple ascending doses of inhaled AR-501

Also known as: Inhaled Gallium Citrate

AR-501 inhaled

Inhaled Placebo DRUG

single and multiple ascending doses of inhaled placebo

Also known as: Control (inhaled placebo)

inhaled AR-501 Placebo

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent given by the subject.
• At least ≥ 18 years old and \< 50 years of age.
• Healthy with no acute medical condition for ≥ 2 weeks prior to screening and no known chronic medical condition requiring regular medical follow up and care.
• Body mass index (BMI) between 18 and 30 kg/m2, inclusive.
• Currently nonsmoking and no history of using nicotine/tobacco-containing products for ≥ 5 years prior to screening.
• Normal chest X-ray, per opinion of the Investigator.
• FEV1 ≥ 80% of predicted values.
• No history or current illicit, pharmaceutical drug or alcohol abuse within ≤ 5 years prior to screening.
• A female subject must meet one of the following criteria:
• If of childbearing potential - agrees to use one of the accepted contraceptive regimens from at least 30 days prior to the first administration of the study medication, during the study, and for at least 90 days after the last dose of the study medication. An acceptable method of contraception includes one of the following:
• Abstinence from heterosexual intercourse
• Hormonal contraceptives (birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch)
• Intrauterine device (with or without hormones), OR
• Agrees to use a double barrier method (e.g., condom and spermicide) during the study and for at least 90 days after the last dose of the study medication
• If a female of non-childbearing potential, the subject should be surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses), as confirmed by follicle stimulating hormone (FSH) levels.

You may not qualify if:

• None of the following criteria can be met.
• Female subjects who are currently pregnant or lactating.
• Oral temperature above 37.5ºC at the time of screening or prior to randomization.
• Clinically abnormal renal function, evidenced by serum creatinine \> 1.5 mg/dL.
• Need for using any nephrotoxic agents during the study.
• Known allergy or hypersensitivity to albuterol.
• Significantly abnormal liver function:
• Total bilirubin \>1.5 x upper limit of the normal range (ULN),
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 3 x ULN and alkaline phosphatase (ALP) \> 2 x ULN
• Hemoglobin \<10 g/dL
• Abnormal corrected serum calcium concentration prior to enrollment.
• History or current use of illicit, pharmaceutical drug or alcohol abuse within 5 years prior to screening.
• Positive urine screen for alcohol, cotinine and/or drugs of abuse at screening and admission.
• Positive test results for Human Immunodeficiency Virus (HIV)-1/HIV-2 antibodies, Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibody (HCVAb).
• Inability to comply with any study requirements based on judgement of the Investigator.

Sponsors & Collaborators

• Aridis Pharmaceuticals, Inc.: lead

Study Sites (25)

Research Site

Tucson, Arizona, 85724, United States

RECRUITING

Research Site

Long Beach, California, 90806, United States

RECRUITING

Research Site

Denver, Colorado, 80206, United States

RECRUITING

Research Site

Gainesville, Florida, 32610, United States

RECRUITING

Research Site

Hollywood, Florida, 33021, United States

RECRUITING

Research Site

Miami, Florida, 33136, United States

RECRUITING

Research Site

Orlando, Florida, 32803, United States

RECRUITING

Research Site

Tampa, Florida, 33606, United States

RECRUITING

Research Site

Chicago, Illinois, 60093, United States

RECRUITING

Research Site

Iowa City, Iowa, 55242, United States

RECRUITING

Research Site

Overland Park, Kansas, 66212, United States

COMPLETED

Research Site

Louisville, Kentucky, 40202, United States

RECRUITING

Research Site

Portland, Maine, 04102, United States

RECRUITING

Research Site

Baltimore, Maryland, 21204, United States

RECRUITING

Research Site

Detroit, Michigan, 48201, United States

RECRUITING

Research Site

Omaha, Nebraska, 68198, United States

RECRUITING

Research Site

New York, New York, 10532, United States

RECRUITING

Research Site

Cleveland, Ohio, 44106, United States

RECRUITING

Research Site

Columbus, Ohio, 43205, United States

RECRUITING

Research Site

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Research Site

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Research Site

Tyler, Texas, 75708, United States

RECRUITING

Research Site

Salt Lake City, Utah, 84132, United States

RECRUITING

Research Site

Seattle, Washington, 98195, United States

RECRUITING

Research Site

Spokane, Washington, 99204, United States

RECRUITING

MeSH Terms

Conditions

Cystic Fibrosis; Pseudomonas Infections

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Hasan S Jafri, MD, FAAP

  Aridis Pharmaceuticals, Inc.

  STUDY DIRECTOR

• Alan H Cohen, MD

  Aridis Pharmaceuticals, Inc.

  STUDY DIRECTOR

Central Study Contacts

Lynne M Deans, MT

CONTACT

4083851742; clinicaltrial@aridispharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a standard double-blind randomized controlled trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is a dose-escalation, placebo-controlled study where subjects are randomized to receive study drug or placebo. SAD and MAD HV Phases: The HV SAD and MAD will each include up to 24 adult subjects in 3 groups (8 per dose group) in each the SAD and MAD phase . All subjects will be randomly assigned in a 3:1 ratio to receive a single administration of active drug (12 HVs) or placebo (4 HVs). The CF MAD will evaluate 4 different dose levels in a total of 54 adult CF subjects (10 per dose level). The first 3 subjects (sentinel subjects) in the low, medium and high dose level will be randomly assigned at a 2:1 ratio to receive either AR-501 or placebo, for a total of 9 CF subjects. An expanded cohort will randomize 30 adult subjects at a 2:3:3:2 ratio to three doses of inhaled AR-501 or placebo. Subsequently an 80mg Ga dose (top dose) cohort will randomize subjects at a 2:1 ratio to receive either AR 501 or placebo for a total of 15 subjects , including 6 sentinel subjects.

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: September 13, 2018
• Study Start: December 7, 2018
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: March 9, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (25)